Our objective is a better understanding of the role of genetic and environmental factors in human neuropsychiatric disorders through the study of the specific disorder, Gilles de la Tourette's syndrome (TS). For nearly a century after its original description in 1885, TS was considered a rare neuropsychiatric disorder. However, recent research has led to several notable advances: 1) a greater understanding of the range of phenotypic expression for the syndrome; 2) a realization that TS and related conditions are much more common than had previously been considered; and 3) a better understanding of the transmission of the disorder. It prevalence and its debilitating effect on those afflicted makes the syndrome a major public health problem. Understanding the genetics of TS will be of direct benefit to patients concerned about recurrence in their families; ultimately, clarifying the genetics of TS may elucidate its pathogenesis. As part of an ongoing family study designed to study the genetics of TS, data from over 90 families have been collected. Data from 65 families have been analyzed. Because our preliminary analyses suggest that there is an etiologic relationship between TS and OCD and that the mode of transmission of TS and related disorders is consistent with autosomal dominant inheritance, we are proposing to increase the number of families being studied to examine several specific hypotheses. We will expand our sample to include 40 families of OCD probands so that it will be possible to characterize more completely the nature of the relationship between TS and OCD. In addition, 15 families of TS probands will be studied intensively for a genetic linkage study. We will obtain blood samples from all living relatives so that the DNA from the lymphocytes can be typed for restriction fragment length polymorphisms. The linkage data will allow us to confirm our findings from segregation analyses and to isolate and characterize any genetic locus. Finally, we plan to initiate a prospective study of young unaffected children who have first degree relatives affected with TS. Forty families with young children have been identified and are available for study. This study will help to identify "non-genetic" factors important for onset and variable expressions of the disorder. Data from these new subject samples will help identify specific genetic and environmental factors associated with the variable expression of TS and related behaviors. In all cases, information will be obtained by direct structured interview.